Introduction

Uses for Acebutolol Hydrochloride

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1280500

β-Adrenergic blocking agents (β-blockers) generally not preferred for initial management of hypertension, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).361501502503504515523524527800

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.355359360500501504 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500

BP Monitoring and Treatment Goals

When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500501

Administration

Acebutolol hydrochloride is administered orally.12 Also been administered IV†,2527282941191192196200202203266 but a parenteral dosage form is currently not commercially available in the US.

Oral Administration

Hypertension

Usually administer as a single daily dose;1245 however, for 24-hour BP control, some patients may require administration of the daily dose in 2 divided doses.1142143144145149155500

Ventricular Arrhythmias

Twice-daily dosing of the drug appears to be more effective than once-daily dosing for the suppression and prevention of frequent VPCs.4185186188189195198199203204248

Angina

Once-daily administration may be as effective as divided doses;4208249 however, further studies are needed.4

Dosage

Available as acebutolol hydrochloride; dosage expressed in terms of acebutolol.1

Adults

Hypertension

Oral

Initially, 200–400 mg daily.1245321 Usual maintenance dosage is 400–800 mg daily, 1140142143144145149150151152153154245246247500 but some patients may achieve adequate BP control with dosages as low as 200 mg daily.14500 Increase dosage up to 1.2 g daily in 2 divided doses in patients with more severe hypertension or if adequate reduction of BP does not occur;124140142143144145149150151152154155 alternatively, add another hypotensive agent (e.g., thiazide diuretic).124142144157158160161165166168

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Adjust dosage of β-blockers according to clinical response4205 and to maintain a resting heart rate of 55–60 bpm.211216

Prescribing Limits

Adults

Hypertension

Oral

Maximum 1.2 g daily.124140142143144145149150151152154155

Special Populations

Renal Impairment

Active metabolite (diacetolol) eliminated principally by the kidneys;1123125 dosage and/or frequency of administration must be modified in response to the degree of renal impairment.1286123124125126127

Cautions for Acebutolol Hydrochloride

Contraindications

Warnings/Precautions

Warnings

Heart Failure

Possible precipitation of heart failure.1

Avoid use in patients with decompensated heart failure; use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).1

Abrupt Withdrawal of Therapy

Possible exacerbated angina symptoms or precipitation of MI in patients with CAD.1 Abrupt discontinuance of therapy is not recommended.1276 Gradually decrease dosage over a period of about 2 weeks; monitor patients carefully and advise to temporarily limit their physical activity.1276 If exacerbation of angina occurs, reinstitute therapy promptly and initiate appropriate measures for the management of unstable angina pectoris.1

Peripheral Vascular Disease

Possible reduction in cardiac output and precipitation or aggravation of symptoms of arterial insufficiency.1 Use with caution; observe for evidence of disease progression.1

Bronchospastic Disease

Possible bronchoconstriction.1

Use with caution in patients with bronchospastic disease; administer the lowest effective dosage (initially in divided doses). A bronchodilator (e.g., a β2-adrenergic agonist, theophylline) should be available for immediate use, if necessary.1

Major Surgery

Possible risks associated with general anesthesia (e.g., severe hypotension, maintenance of heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.1 Use with caution in patients undergoing major surgery involving general anesthesia; anesthetics used should not cause myocardial depression.1

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.1 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.1

Sensitivity Reactions

Anaphylactic Reactions

Patients with a history of anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blocking agents.1 Such patients may be unresponsive to usual doses of epinephrine.1

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in higher concentrations than in maternal plasma.12105 Use not recommended by manufacturer.1

Pediatric Use

Safety and efficacy not established in children <12 years of age.1268

Geriatric Use

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger adults.1 However, reduction of maintenance dosage may be necessary,12 since bioavailability of acebutolol and diacetolol (active metabolite) may be increased compared with that in younger adults.12122 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution.12 Cirrhosis does not appear to substantially affect the pharmacokinetics of acebutolol or diacetolol; however, the effects of hepatic impairment on elimination of the drug have not been fully evaluated.128

Renal Impairment

Use with caution; dosage should be reduced based on the degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Food

Food may slightly decrease the rate of absorption and peak plasma concentrations of acebutolol and its major metabolite (diacetolol), but the extent of absorption is not substantially affected.12101

Onset

Effect on resting, reflex, or exercise-induced heart rate and systolic BP begins within 1–1.5 hours,132191100 in healthy12198100 or hypertensive91 individuals.

Duration

Effect may persist for up to 24 hours or longer.139198100

Special Populations

In geriatric patients, peak plasma concentrations and AUCs of acebutolol and diacetolol are increased twofold compared with those observed in younger patients.12122

Distribution

Extent

Acebutolol and diacetolol readily cross the placenta12105106107 and can accumulate in the fetus.105106107

Acebutolol and diacetolol are distributed into milk at concentrations higher than those in maternal plasma. (See Lactation under Cautions.)12105106

Plasma Protein Binding

Approximately 11–25% (acebutolol) and 6–9% (diacetolol).293103 Approximately 50% bound to erythrocytes.4125

Elimination

Metabolism

Rapidly and extensively metabolized in the liver2110113 to metabolites (acetolol and diacetolol).24699108109110113

Elimination Route

Acebutolol and its metabolites are excreted in feces and urine.18792109111123

Half-life

About 3 hours in the initial distribution phase (t½α) 95 and about 11 hours (range: 6–12 hours) in the terminal phase (t½β).95125 About 7.5 (range: 7–11 hours) and 3 hours, respectively, for diacetolol and acetolol following a single oral dose.101108125

Special Populations

Renal impairment may reduce clearances of acebutolol and diacetolol.125 Acebutolol and diacetolol are removed by hemodialysis.1125127

Stability

Storage

Oral

Capsules

Tight containers1253 at room temperature (approximately 25°C).123

Protect from light.1305

Actions

Pharmacologic effects result from both the unchanged drug and diacetolol, 12114115116117 which is equipotent to acebutolol.12114115116117

Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium.12456789101112131415161718192021222324252627283435363738 Blocks β2-adrenergic receptors within bronchial and vascular smooth muscle only at high doses.42435178

Decreases exercise-induced heart rate,12411121323242527 inhibits reflex orthostatic tachycardia,1241112132324 and may decrease12252829140193 or leave unchanged 26140 cardiac output at rest225140193 or during exercise.12829 Decreases systolic and diastolic BP at rest121319235657139 and during exercise.12155160171

95. Gulaid AA, James IM, Kaye CM et al. The pharmacokinetics of acebutolol in man, following the oral administration of acebutolol HCl as a single dose (400 mg), and during and after repeated oral dosing (400 mg, b.d.) Biopharm Drug Dispos. 1981; 2:103-14.

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311. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265:3255-64.

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349. Williams CL, Hayman LL, Daniels SR et al. Cardiovascular health in childhood: a statement for health professional from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2002; 106:143-60.

355. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)

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